Ozone at environmentally relevant concentrations induce subtle changes in the pulmonary epithelial lining at the junction of the terminal bronchiole and alveolar duct. Alveolar macrophage numbers also increase in this region of the lungs following exposure to ozone. Whether these changes represent an adverse health effect is unknown. To address this question, preliminary studies were done in rats exposed to simulated pattern of "ambient" ozone at environmentally relevant concentrations for weeks followed by a single 5 hour exposure to asbestos fibers. The deposition of fibers in the lungs was similar for both ozone-exposed and air-exposed animals immediately following the end of asbestos exposure, but by one month postexposure, fiber retention was three-fold greater in animals pre-exposed to ozone compared to control animal These findings suggest that low level exposure to ozone strongly compromises the lung's ability to remove respired particulates and may represent an unexpected detriment effect of ozone adaptation. The objective of Project 6 is to examine the interactive effects of particles with aerosols and ozone on acute and chronic lung injury. A major emphasis will be to examine whether ozone at environmentally relevant concentrations adversely affect the lung's ability to respond to particulates and aerosols. An inert particle, carbonyl iron, will be used along with sulfuric acid mists. To elucidate the effects of ozone on particle uptake and retention in the lungs, the use of carbonyl iron should be more relevant than a toxic fiber such as asbestos. We will focus our studies on the centriacinar region where distal airways join the proximal alveolar region of the lungs. Species used in this study will be rats and monkeys. Rats represent the most commonly used species in studies of pulmonary effects of ozone and form the largest repository of information for comparison to the proposed studies. Monkeys have extensive respiratory bronchiole system similar to that found in the human lung an provides the means by which extrapolation of the proposed studies to the human is possible. Initial studies conducted in rats will provide direction for later studies in monkeys. The first phase of the project will examine deposition, clearance an retention of acute and long-term exposures to ozone and particles. The second phase will evaluate simultaneous challenges of ozone and acid aerosols for effects on the properties of the pulmonary epithelium. The third phase will test ozone-acid aerosol effects on particulate clearance.